Final: Primary Immunodeficiencies Flashcards
What is the pathology behind B cell deficiencies? What are you more susceptible too?
- Absent or reduced follicles and germinal centers in lymphoid organs
- Reduced serum Ig levels
Susceptible to bacterial and viral infections
What is the pathology behind T cell deficiencies? What are you more susceptible too?
- Reduced T cell zones in lymphoid organs
- Reduced DTH reactions
- Defective T cell proliferative responses
Susceptible to intracellular and viral infections + cancers
What is the pathology behind innate immunity deficiencies? What are you more susceptible too?
Really depends on what is defective
Susceptible to bacterial and viral infections
What are some key features of immunodeficiencies?
- Chronic, severe, recurrent
- Not responsive to antibiotic therapy
- Atypical microbes and opportunistic pathogens involved
What are Primary Immune Immunodeficiencies?
- Manifested in first years of life after maternal immunoglobulins disappear
- Can be defects in innate or adaptive immunity
Why would you screen for humoral immunity?
Recurrent sinopulmonary bacterial infections
Why would you screen for cell-mediated immunity?
Recurrent viral/fungal infections
Why would you screen for phagocyte deficiency?
Recurrent skin abscesses/fungal infections
Why would you screen for complement deficiency?
Bacteremia
Meningitis with encapsulated bacteria
What lab test would you order for adaptive immunity deficiency?
Differential count of blood cells (Complete CDC)
What lab test would you order for T-cell deficiency?
DTH skin test
What lab test would you order for humoral deficiency?
Serum Antibody Count
Ab testing to specific Ag
What lab test would you order for complement deficiency?
Total hemolytic complement assay
What lab test would you order for phagocytic deficiency?
Nitroblue Tetrazolium Test
What is SCID?
Reduced T Cell, B Cell, and NK Cells
- present with persistent infections, oral thrush, chronic diarrhea, and failure to thrive
- Severe lymhphopenia
- As a fetus, risk of abortion from maternal T cells
What are the different immunophenotypes for SCID?
T-B-NK-: Adenosine-deaminase Deficiency
T-B-NK+: Artemis or RAG 1/2 Deficiency
What is Adenosine Deaminase Deficiency?
T-B-NK-
- ADA important for adaptive immunity maintenance and development (especially T cells)
- Without ADA, build-up of deoxyadenosine, which is toxic
- Low Ig count
- Autosomal recessive disorder
What is Purine Nucleoside Phosphorylase Deficiency?
T- B+/- NK+/-
- Accumulation of dGTP, which is toxic
- Early onset of neurological abnormalities
- Autoimmune disorders are common: hemolytic anemia, thyroid disease, arthritis, lupus
What is Artemis Deficiency?
T- B- NK+
- Artemis is important for repairing double strand breaks and an enzyme in VDJ recombination
- Diarrhea, candidiasis, Pneumocystis jiroveci pneumonia
What is Rag 1 and Rag 2 Deficiency?
T- B- NK+ and Low Ig
- Impaired VDJ recombination
- Diarrhea, candidiasis, Pneumocystis jiroveci pneumonia
- Can lead to Omen Syndrome: severe erythroderma, splenomegaly, eosinophilia, high IgE
What is Jak3 Deficiency?
T- B+ NK+
- Mutation in Janus Kinase 3
- Defect in Il-2 signaling
- Autosomal Recessive
What is agammaglobulinemia?
B cell development is arrested at Pre-B stage
- very few circulating B cells
- mostly X-linked but can be autosomal recessive
What is X-linked Btk Kinase Deficiency?
Mutation in a tyrosine kinase that causes a defect in rearrangement of Ig Heavy Chains
No IgM, IgG, or IgA serum antibodies
What are Isolated IgG deficiencies?
Decreased concentrations of IgG subclasses
- Associated with recurrent viral/bacterial infections in respiratory tract
- Normally low levels of IgG2
